Despite extensive research in the last decades, the pathophysiology of bipolar disorder (BD) remains unclear. Access to post-mortem brain tissue of subjects who had BD offers an opportunity to investigate neurobiology and this approach has led to some progress, particularly, due to the availability of more sophisticated molecular and cellular biological methodologies and well characterized brain collections over the past decade. Here we review the findings of morphometric post-mortem studies in BD and interpret them in the context of a potential physiopathological mechanism involving oxidative stress and apoptosis. A review of the literature was conducted to identify post-mortem studies that investigated cellular changes such as number, density and size of neurons and glia, in brains of subjects with BD. We found decreased density of neurons and glia and decreased size of neurons in frontal and subcortical areas of the brain. Based on recent studies that found evidence of increased apoptosis and oxidative stress in BD, we hypothesize that the cell abnormalities described are due to an increase in the apoptotic process that can be triggered, through its intrinsic pathway, by the existence of an exacerbated production of reactive oxygen species and oxidative damage in the disease.

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Summary.The quantitative postnatal changes of the cerebella of 65 Wistar rats aged 2-120 days have been examined. The cerebellar volume increases in two phases: The first phase lasts from birth to the seventh postnatal week. The second phase begins ten weeks post parturn and lasts for a Ionger period than the first phase.The cerebellar surface increases continuously from birth to the end of the seventh week.The volume of the external granular layer is maximal when the organ grows rapidly. The external granular layer has nearly disappeared 24 days after birth; the volume of the interaal granular layer is maximal at this time. Later on, the volume and the width of the interaal granular layer decrease. Myelinization of the cerebellar fibers and growth of the molecular layer run parallel to this decrease. The second late, but protracted growth of the cerebellum, ten weeks after birth, is due to an increase of the molecular and medullary layer. These findings are in good accord with histological, histochemical, and ultrastructural observations of other authors.

Summary. The ultrastructure of autofluorescent, PAS-positive lipofuscin in Purkinje, granule, Golgi epithelial, basket and stellate, microglial and perivascular cells in the cerebellar cortex of senescent rats is described. The membrane-bounded pigment is composed ofthree elements: 1) electron-lucent homogeneaus droplets, 2) a granular matrix and 3) intensely osmiophilic patches. The proportians ofthese three components vary between cell types and one can grossly differentiate a neuronal and a gliallipofuscin. The lipofuscin granules of stellate and perivscular cells are different from lipofuscin of other cerebellar neurons and glia. lt can be concluded from these morphological observations that each cerebellar cell type has its distinct lipofuscin.

Summary. Valurne densities, surface densities, length densities and numerical densities of several structures in the neocerebellar lobtde VIa and the archicerebellar lobule X of six-month old male Han: WIST -rats were estimated by point-and intersection-counting. The volume densities of dendritic spines (ca. 6.5%), parallel fiber varicosities (ca. 25°/o) and processes of Bergmann glial cells ( ca. 21 %) were similar in the upper third ofthe molecular layer oflobule VIa and X respectively. The surface density of the spine membrane was 31 mm 2 /mm 3 in lobule X and 32 mm 2 /mm 3 in lobule VIa {p=0.4375; paired Pitman permutation test).The length density of dendritic spines varied from 793 meters/mm 3 in lobule VIa to 675 meters/mm 3 in lobule X {p=0.0938). The mean caliper diameter of parallel fiber-Purkinje cell synapses was estimated by Mayhew's (1979) method and calculated by Cruz-Orive's (1983) computer pro gram. Both tests yielded nearly identical numerical densities of parallel fiber synapses in lobule VIa (6.558 x 10 8 jmm 3 ) and in lobule X (4.892 x 10 8 /mm 3 ; p = 0.0313). The area of synaptic apposition relative to the postsynaptic dendritic spine surface was higher in lobule VIa (13.3o/o) than in lobule X (10.4o/o; p =0.0313). The data provide electron microscopic evidence of regional differences in spine morphology, which tagether with different spiny branchlet diameter and numerical density of parallel fiber synapses may be of importance in Purkin je cell physiology.Key words: Cerebellar cortex -Albino rats -Quantitative anatomyPurkinje cells -Spines -Parallel fiber synapses -Regional differences lntroduction The dendritic trees of Purkin je cells display their full ramification in a vertical plane at right angles to the longitudinal axis of the cerebellar lobule.